Massively out of form in the Premier League, Alan Pardew's men are destined for relegation but the club may aim to save their campaign somewhat by progressing in the prestigious competition.
Whereas Southampton are among seven-ten teams who could realistically be within the drop scrap come the end of the season, and with an abundance of criticism a burden on his shoulders; Mauricio Pellegrino will want to save his job on the south coast.
The two outfits last met in the top-flight earlier this month when an early opener from the Baggies was cancelled out via goals courtesy of Mario Lemina, James Ward-Prowse and Jack Stephens to ensure the three points went back to St. Mary's.
Marquee January arrival out for Baggies
West Brom have suffered a major injury problem in their attacking options as Daniel Sturridge, on loan from Liverpool, was substituted after a measly three minutes into the club's defeat to Chelsea last Monday.
As for fellow winter transfer window acquisition, Ali Gabr, also on loan, from Egyptian side Zamalek, has received international clearance and could feature for the visit of Southampton.
Striking shortages for Pellegrino
Saints manager Mauricio Pellegrino has an increasing headache for lack of goals in forthcoming matches as Charlie Austin remains on the sidelines and fellow forward Shane Long joins his team-mate in the stands with a hamstring injury.
Meaning Manolo Gabbiadini or Guido Carrillo are likely to see their name in the starting eleven, and other than that, the boss may name an unchanged team to the one which lost to Liverpool on Sunday.
First cup encounter in nearly 40 years
West Bromwich Albion and Southampton have met on numerous occasions in the League Cup and top-flight, however, it hasn't been since 1979 that the two outfits have encountered each other in the FA Cup.
The Saints hosted the Baggies that day in a fifth round replay when goals via Phil Boyer and David Peach were enough to advance the Hampshire club into the next round.